On April 8, 2022 SimBioSys, the technology company that predicts tumor responses to therapy, reported it will present nine posters at the AACR (Free AACR Whitepaper) Annual Meeting 2022, taking place in New Orleans from April 8-13 (Press release, SimBioSys, APR 8, 2022, View Source [SID1234611734]). The posters will show the breadth of applications for the platform, from clinical uses in evaluating existing treatment options for patients with breast cancer, to metabolic profiling of solid tumors such as breast, prostate, and pancreatic cancers, as well as melanoma.

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SimBioSys will showcase TumorScope at the AACR (Free AACR Whitepaper) for the first time in a poster session on April 11. The biophysical simulation platform allows physicians and patients to better visualize and understand cancer and predict treatment response using only standard of care data to select the best possible therapy based on the patient’s own unique biology.

"As the number of oncology therapeutics continues to increase, it is of critical importance to have tools like TumorScope that can accurately predict patient outcomes prior to therapy to facilitate effective personalized care," said Tushar Pandey, CEO of SimBioSys.

At AACR (Free AACR Whitepaper), the company will present data on an independent validation study of TumorScope in collaboration with the University of Cincinnati. The study demonstrates how TumorScope predicts the pathological complete response (pCR) in breast cancer patients using only standard of care diagnostic data with an accuracy above 90 percent. This robust performance was observed across all breast cancer subtypes.

The utility of TumorScope transcends the clinic, where another poster highlights the use of the technology in a systems medicine-based approach to perform comprehensive metabolic profiling of various tumor types. The combination of RNA-sequencing data and metabolic network modeling made possible the identification of specific metabolic profiles, potentially key drivers of the tumor response to therapy thereby contributors of patient outcome. The results include data on breast cancer, lung adenocarcinoma, pancreatic adenocarcinoma, metastatic melanoma, clear renal cell carcinoma and salivary cystic adenoid carcinoma. This approach can be utilized as a systematic way to identify metabolic targets for treatment.

These clinical and research application studies, along with data on the biology behind racial disparities in breast cancer and pathology data, will also be presented at the conference.

"We are excited to present our technology and our research for the first time at the AACR (Free AACR Whitepaper)," said Pandey. "It is the ideal platform to showcase Tumor Scope’s utility not only in the clinic, but as a powerful cancer research tool with applicability in drug development."

The full nine abstracts and posters can be found here. For more information on these studies, please visit www.simbiosys.com.

On April 8, 2022 Boundless Bio, a next-generation precision oncology company developing innovative therapeutics directed against extrachromosomal DNA (ecDNA) in oncogene amplified cancers, reported that it will present a new finding at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, held in New Orleans and virtually from April 8-13, 2022 (Press release, Boundless Bio, APR 8, 2022, View Source [SID1234611733]). The poster, Replication stress and the inability to repair damaged DNA, the potential "Achilles’ heel" of ecDNA+ tumor cells, is available to registered attendees online starting today and for in-person presentation on April 11, 2022 at 1:30 PM – 5:00 PM CT.

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"Replication stress has long been known to be a driver of genomic instability in cancer," said Christian Hassig, Ph.D., Chief Scientific Officer of Boundless Bio. "This study demonstrates ecDNA-enabled gene amplified cancers have inherently high replication stress, thereby providing a unique point of intervention for our novel ecDNA-directed therapeutics (ecDTx). This work is an important scientific advancement both in our understanding of gene amplifications on ecDNA and in translating the science into novel therapeutics for patients with gene amplified cancers who currently have few treatment options."

Boundless Bio previously demonstrated that cancers with oncogenes amplified on ecDNA are associated with poor clinical prognosis1 and generally do not respond to targeted therapies, underscoring the urgent need to identify clinical strategies to treat ecDNA amplified cancers. For the first time, we present data showing a relationship between ecDNA and DNA replication stress, a known form of genomic instability that contributes to oncogenesis and tumor evolution. While the drivers of replication stress remain unclear, excessive replication stress leads to extensive DNA damage and cancer cell death. The results demonstrate ecDNA-enabled colorectal cancer cells have intrinsically elevated levels of replication stress and are hypersensitive to replication stress inducing agents. These novel findings highlight replication stress as a potential synthetic lethal approach in ecDNA amplified cancers.

Poster available at Boundless Bio website.

Reference
1Kim, Nguyen, Turner et al. Nature Genetics 2020

About ecDNA

Extrachromosomal DNA ("ecDNA") are circular units of nuclear DNA found within cancer cells, and which contain highly transcriptionally active genes, including oncogenes, but are physically distinct from chromosomes and lack centromeres. ecDNA replicate within cancer cells and, due to their lack of centromeres, can be asymmetrically passed to daughter cells during cell division, leading to focal gene amplification and copy number heterogeneity in cancer. By leveraging the plasticity afforded by ecDNA, cancer cells have the ability to increase or decrease copy number of select oncogenes located on ecDNA to enable survival under selective pressures, including targeted therapy, immunotherapy, chemotherapy, or radiation, thereby making ecDNA one of cancer cells’ primary mechanisms of growth, recurrence, and treatment resistance. ecDNA are not found in healthy cells but are present in many solid tumor cancers. They are a key driver of the most aggressive and difficult-to-treat cancers, specifically those characterized by high copy number amplification of oncogenes.

On April 8, 2022 NiKang Therapeutics Inc. ("NiKang"), a clinical stage biotech company focused on developing innovative small molecule oncology medicines to help patients with unmet medical needs reported presentation of preclinical data investigating NKT2152’s mechanism of action, in vivo pharmacokinetic and pharmacodynamic profile, and anti-tumor effect in multiple xenograft models including ccRCC and hepatocellular carcinoma at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 (Press release, NiKang Therapeutics, APR 8, 2022, View Source [SID1234611732]).

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"The NKT2152 preclinical data presented today highlight its best-in-class potential with excellent potency and PK profile and support the advancement of this molecule into clinical studies," said Zhenhai Gao, Ph.D., Co-founder, President and Chief Executive Officer of NiKang. "The anti-tumor effect observed in several xenograft models suggests NKT2152 may have broader activity in other solid tumors beyond ccRCC that lack a VHL gene deficiency. We will explore such opportunities with the goal of helping more patients in need."

About NKT2152

NKT2152 is a small molecule that inhibits HIF2α. It is currently in a phase 1/2 dose escalation and expansion trial (NCT05119335). This trial is designed to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics and clinical activity in patients with advanced ccRCC. Once an appropriate dose is identified, combination studies including NKT2152 will commence.

On April 8, 2022 Affimed N.V. (Nasdaq: AFMD) ("Affimed", or the "Company"), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported data from the dose escalation phase of the phase 1/2a study with the Company’s Innate Cell Engager (ICE) AFM24 as monotherapy at the Annual Meeting of the American Association of Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Affimed, APR 8, 2022, View Source [SID1234611730]). A poster will be presented on April 11 during the Phase I Clinical Trials 1 session.

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The poster presentation includes data of 29 heavily pretreated patients with a variety of tumors known to express EGFR, who have received AFM24 as weekly infusions across six dose levels from 14 mg to 480 mg. AFM24 demonstrated a well-managed safety profile. The most frequent treatment-emergent adverse events were infusion-related reactions, nausea and headache. Stable disease was observed as best response in 8 of 24 response-evaluable patients.

The pharmacokinetic and CD16A receptor occupancy data demonstrate good target engagement at doses of 320 mg and 480 mg. Pharmacodynamic activity was observed at doses of 160 mg and higher. The recommended phase 2 dose was determined at 480 mg based on safety and tolerability, exposure and CD16A receptor occupancy. The maximum tolerated dose was not reached by the treatment regimen up to 480 mg. Enrollment in the dose escalation has continued at a dose of 720 mg for the purpose of collecting additional data on safety and tolerability.

"Having reached a safe and well-tolerated recommend phase 2 dose with pharmacologic and pharmacodynamic activity is a major milestone for the AFM24 program," said Dr. Andreas Harstrick, Chief Medical Officer at Affimed. "This has been important for the initiation of a broad development program assessing the efficacy of AFM24 as monotherapy and in combinations, and we’re planning to provide first updates on the studies in 2022."

Affimed is enrolling patients in three open label phase 1/2a studies, evaluating the activity of AFM24 as monotherapy (AFM24-101), and in combination with Roche’s anti-PD-L1 checkpoint inhibitor atezolizumab (AFM24-102) as well as in combination with SNK01, NKGen Biotech’s NK cell product (AFM24-103).

The abstract and poster are electronically accessible for participants of the AACR (Free AACR Whitepaper) conference following this link: https://bit.ly/3ukFMqc

An update of another ICE, AFM13, combined with cord blood-derived NK cells in patients with CD30-positive lymphoma will be presented on Sunday, April 10, 1:00 – 3:00 p.m. CST in the session Clinical Trials of Cellular Immunotherapies.

About AFM24
AFM24 is a tetravalent, bispecific innate cell engager (ICE) that activates the innate immune system by binding to CD16A on innate immune cells and EGFR, a protein widely expressed on solid tumors, to kill cancer cells. Generated by Affimed’s fit-for-purpose ROCK platform, AFM24 represents a distinctive mechanism of action that uses EGFR as a docking site to engage innate immune cells for tumor cell killing through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.
Affimed is evaluating AFM24 as a monotherapy (AFM24-101) for patients with advanced EGFR-expressing solid malignancies whose disease has progressed after treatment with previous anticancer therapies. The first-in-human Phase 1/2a open-label, non-randomized, multi-center, multiple ascending dose escalation and expansion study and can be found at www.clinicaltrials.gov using the identifier NCT04259450. Furthermore, AFM24 is evaluated in a phase 1/2a study in combination with Roche’s anti-PD-L1 checkpoint inhibitor atezolizumab (AFM24-102, NCT05109442). Affimed and NKGen Biotech have initiated a Phase 1/2a study , investigating AFM24 in combination with SNK01, NKGen Biotech’s NK cell product (AFM24-103, NCT05099549).

On April 8, 2022 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported the results of preclinical studies evaluating the anti-cancer activity of onvansertib in combination with the PARP inhibitor (PARPi) olaparib in PARPi-resistant patient-derived xenograft (PDX) ovarian cancer models (Press release, Cardiff Oncology, APR 8, 2022, View Source [SID1234611729]). The results are featured in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which is taking place both virtually and in-person at the Ernest N. Morial Convention Center in New Orleans, Louisiana from April 8-13, 2022.

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"In these studies, we sought to evaluate how combining onvansertib with PARP inhibition, an approved maintenance treatment for ovarian cancer, might mitigate the known phenomenon of acquired tumor resistance to PARP inhibitors," said Tod Smeal, Ph.D., chief scientific officer at Cardiff Oncology. "We are very pleased with the results, which showed onvansertib and olaparib synergistically combining to generate strong activity against PARPi-resistant patient-derived ovarian cancer models. Given the current lack of effective treatment options for patients showing PARPi resistance, we believe these data are supportive of evaluating this combination within a PARPi-resistant clinical setting."

Preclinical studies featured in the AACR (Free AACR Whitepaper) poster evaluated onvansertib-olaparib combination treatment in three olaparib-resistant patient-derived xenograft (PDX) ovarian cancer models. Two of the three PDX models used (MNHOC22, MNHOC266) were cisplatin-sensitive with a mutated BRCA1 gene, while the third (MNHOC316DDP) was cisplatin-resistant with wild type BRCA1. BRCA1-mutant tumor cells are deficient for homologous recombination (HR)-mediated DNA repair and are initially sensitive to PARPi. This suggests that PARPi resistance was acquired in the MNHOC22 and MNHOC266 tumors due to the restoration of HR-mediated DNA repair, while being naturally conferred in MNHOC316DDP tumors due to continuous HR-proficiency.

Data showed that combining onvansertib with olaparib led to a statistically significant survival benefit compared to treatment with either agent alone in each of the three evaluated PDX models. Results showed the combination was well tolerated.

An electronic copy of the poster and corresponding abstract, entitled, Combining PARP inhibition with the Polo-like kinase 1 (PLK1) inhibitor onvansertib overcomes PARP inhibitor resistance, is available to registered attendees of the AACR (Free AACR Whitepaper) annual meeting on the meeting website. The in-person presentation will take place during the "Drug Resistance and Reversal of Resistance" poster session on April 12, 2022, from 1:30 PM – 5:00 PM CT. Following the meeting, the poster will be available on the "Scientific Presentations" section of the Cardiff Oncology website at View Source